Treatment Modality For Prostate Cancer Research Articles

125I brachytherapy for localized prostate cancer: a single institution experience.

To evaluate the clinical outcome of a cohort of localized prostate cancer patients treated with 125I permanent brachytherapy at the University of Turin. A retrospective analysis was carried out on 167 consecutive patients with early stage prostate adenocarcinoma who underwent 125I brachytherapy between January 2003 and December 2010. A minimum follow-up of ≥ 12 months was mandatory for inclusion. Biochemical disease-free survival (defined on the basis of the ASTRO definition and the ASTRO-Phoenix definition) was chosen as the primary end point. Secondary end points were gastrointestinal and genitourinary toxicity (acute and late, defined according to the RTOG scale). With a median follow-up of 42 months (range, 13.5-90.7), biochemical disease-free survival at 3 and 5 years was respectively 91.1% and 85.7%, according to the ASTRO definition and 94.5% and 85.1% according to ASTRO-Phoenix definition (for statistical purposes, only the ASTRO definition was used). Hormone treatment and nadir PSA (cutoff of 0.35 ng/ml) were the only factors affecting biochemical disease-free survival both on univariate (P = 0.02 and P = 0.001, respectively) and multivariate analysis (HR 0.024; P = 0.021 and HR 21.6; P = 0.006, respectively). Only 3.6% of patients experienced ≥ grade 3 acute urinary toxicity and 5% ≥ grade 3 late urinary toxicity. Prior transurethral prostate resection was the only independent predictor of grade 3 late urinary toxicity on multivariate analysis (HR 0.13; P = 0.009). This mono-institutional series confirmed that brachytherapy is an effective and safe treatment modality for localized prostate cancer, with acceptable short- and long-term morbidity rates.

Treatment modalities for intermediate risk prostate cancer: surgery vs hypofractionation RT vs focal therapy vs active surveillance

Treatment modalities for intermediate risk prostate cancer: surgery vs hypofractionation RT vs focal therapy vs active surveillance

Treatment modalities for intermediate risk prostate cancer: surgery vs hypofractionation RT vs focal therapy vs active surveillance

Treatment modalities for intermediate risk prostate cancer: surgery vs hypofractionation RT vs focal therapy vs active surveillance

Prostate cancer: updates on current strategies for screening, diagnosis and clinical implications of treatment modalities.

Prostate cancer is the most common cancer in men by way of diagnosis and a leading cause of cancer-related deaths. Early detection and intervention remains key to its optimum clinical management. This review provides the most updated information on the recent methods of prostate cancer screening, imaging and treatment modalities. Wherever possible, clinical trial data has been supplemented to provide a comprehensive overview of current prostate cancer research and development. Considering the recent success of immunotherapy in prostate cancer, we discuss cell, DNA and viruses based, as well as combinatorial immunotherapeutic strategies in detail. Furthermore, the potential of nanotechnology is increasingly being realized, especially in prostate cancer research, and we provide an overview of nanotechnology-based strategies, with special emphasis on nanotheranostics and multifunctional nanoconstructs. Understanding these recent developments is critical to the design of future therapeutic strategies to counter prostate cancer.

Impact of Prostate Cancer and Its Treatment on the Outcomes of Ileal Pouch-Anal Anastomosis

There are scant published data in the impact of prostate cancer and its treatment on functional outcomes and quality of life (QOL) in patients with ileal pouch-anal anastomosis (IPAA). The aim of the study was to evaluate the influence of prostate cancer and its treatment on functional outcomes and QOL in patients with IPAA. Patients with IPAA with prostate cancer were compared to age and pouch duration-matched controls without prostate cancer in a 1:2 ratio. Pouch function and QOL were compared between pretreatment and posttreatment for prostate cancer as well as between subjects and controls. A total of 30 patients with IPAA with prostate cancer and 60 matched controls were included. Treatment modalities of prostate cancer included prostatectomy (n = 22), brachytherapy (n = 5), watchful waiting (n = 2), and hormonal therapy (n = 1). The median length of follow-up was 6 (interquartile range, 2.7-8) years. Permanent fecal diversion was required in 5 (16.7%) patients with prostate cancer who developed pouch failure, as compared with 2 patients in the control group (P = 0.04). In patients who retained their pouches, the pouch functional outcomes at the latest follow-up were similar to that before prostate cancer treatment and to that of the matched controls, in terms of bowel movements, daytime seepage, nighttime bowel movements, nighttime seepage, and QOL score. The risk of pouch failure may be increased after the diagnosis of prostate cancer with or without treatment. However, for those with retained pouches, their pouch function and QOL did not seem to be adversely affected.

Hypermethylation of the SPARC promoter and its prognostic value for prostate cancer

Secreted protein acidic and rich in cysteine (SPARC) is a secreted matricellular glycoprotein and plays a key role in the development of many tissues and organ types. However, the role of SPARC in prostate cancer (PCa) is still controversial. The aim of the present study was to investigate the abnormalities in the expression of SPARC and its promoter hypermethylation in prostate cancers and in correlated clinicopathological profiles. We examined the hypermethylation of the SPARC promoter as a potential mechanism for suppressing SPARC in PCa. The clinicopathological correlation between SPARC and its promoter expression and the prognostic significance of the aberrantly expressed genes were evaluated to identify novel biomarkers of PCa. SPARC expression was decreased in PCa cell lines, which correlated with hypermethylation of the SPARC promoter. Treatment with the demethylating agent 5-Aza-Cdr restored SPARC expression. Seventy percent (145 of 207) of the primary tumors exhibited SPARC hypermethylation, while only 2.6% was found in normal prostate mucosa (n=38). In PCa cases, SPARC hypermethylation was correlated with a poorer prognosis (P=0.005; relative risk 2.659, 95% CI, 1.433‑4.562). Our findings revealed potential diagnostic markers of PCa based on specific hypermethylated CpG sites and also provided new insights of SPARC as a novel biomarker and/or treatment modality for prostate cancer.

When Radiation Proctitis Gets Way Complicated

Radiotherapy is an essential treatment modality for prostate cancer. However, radiation proctitis (RP) is a common complication, with 40% developing rectal hemorrhage. Previous successful experiences in treating cystitis has led to the use of formalin as a treatment modality. Although there have been few published reports of formalin use for RP in the literature, most results show that it is safe and effective. Unusual complications such as fistulae, anal stenosis and colitis have been rarely reported. A 61-year-old man with medical history of prostate cancer status-post radiation therapy completed 6 months ago presented with a 2-week history of rectal bleeding and tenesmus. He denied fever, use of antibiotics, weight loss or previous GI bleeding. Digital rectal exam was painful and with evidence of blood clots. Initial labs showed iron deficiency anemia. Patient underwent colonoscopy which showed a large erythematous ulcerated lesion that extended from anal verge up to 10cm and covered 70% of diameter (Figure 1). Histologic exam was consistent with RP and negative for rectal carcinoma. Initially, patient was provided with supportive management with hydration and steroid enemas. However, he developed progression of symptoms with intractable rectal bleeding requiring multiple blood transfusions as well as severe rectal pain. Pelvic MRI showed bilaterally myositis of the obturator internus and pectineus muscles suggestive of radiation induced myositis. Given severity of symptoms, General Surgery proceeded with rectal instillation of 4% formalin which was unsuccessful for which diverting Loop Colostomy was performed. Patient showed improvement of symptoms until a few days later when he developed hematochezia, fever and leukocytosis. Abdominal CT revealed inflammatory colitis suggestive of formalin-induced colitis which resolved with antibiotics and hydration. Follow up colonoscopy was performed for possible re-connecting surgery which showed anal canal stenosis with 99% of lumen occluded (Figure 2). Patient was referred to Colorectal surgeon whom performed multiple dilations with resolution of stenosis. In this case, anal stenosis and colitis were a complication of formalin instillation as therapy for RP. Both complications are very rare and few cases have been published in which a clinical scenario mirroring our patient presentation and outcome are described. Awareness of rarely described complications is essential for early recognition and treatment.Figure: Large erythematous ulcerated lesion.Figure: Anal canal stenosis.

Permanent Seed Brachytherapy for Low Risk Prostate Cancer, Long Term Outcome, and Urinary Toxicity

Low dose rate seed brachytherapy is an established treatment modality for low risk prostate cancer (CaP). Herein, we report long term biochemical control and urinary toxicity from a single institution. Data from a prospectively-collected institutional database was used, completed with retrospective chart reviews. All patients with low-risk CaP (NCCN criteria) who underwent ultrasound-guided permanent iodine-125 brachytherapy from March 1999 to December 2005 were included. Urinary function was evaluated by the International Prostate Symptom Score (IPSS). PSA relapse was defined by Phoenix Criteria (Nadir + 2 ng/ml). Time to IPSS return to baseline score ±3 was recorded. 582 patients with a median age of 64 years were included. Median initial PSA was 5.5 ng/ml (0.3-10). 66% and 34% were T1 and T2a, respectively. Gleason score was 6 (96%) and <6 (4%). Prescription dose was 145Gy, with a median V100 coverage of 94% (IQR [Inter-quartile range] 89-97%) and median D90 of 157Gy (IQR 144-171 Gy). With a median follow up of 131 months (IQR 94-149 months), 27 patients showed biochemical failure (4.6%), and PSA bounce was detected in 38 cases (7%). Biochemical progression-free rates were 97% (96-98%), 96% (94-97%), and 94% (91-96%) at 5, 10, and 15 years, respectively. Median PSA level at 5, 10 and 15 years was 0.06, 0.05 and 0.018 ng/ml, respectively. PSA relapses were observed out to 148 months. At 1, 5, 10 and 15 years, 5.5%, 16.5%, 39.5% and 89.2% of patients were lost to PSA follow up. Median baseline IPSS score was 5. In 515 (88.5%) patients IPSS returned to baseline, with a median time to return-to-baseline of 9 months. The proportion of return-to-baseline at 1, 2, 5, and 10 years was 62%, 75%, 88%, and 90%, respectively. 22 (4%) patients required post-implant urinary catheter. After 3, 6 and 12 months, 9 (1.5%), 6 (1%) and 4 (0.7%) patients continued to be catheterized. Within the limits of retrospective analysis, permanent seed brachytherapy for low risk prostate cancer is an effective treatment modality with low urinary toxicity. Treatment resulted in excellent long-term biochemical control although late relapses were observed.

Highlights of This Issue

Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer therapy that uses an antibody-photoabsorber conjugate (APC) activated by NIR light. NIR-PIT causes minimal damage to non-target tissues and is effective with a variety of antibodies conjugated to the same photoabsorber. Prostate-specific membrane antigen (PSMA) is expressed in more aggressive prostate cancers and is an attractive target for NIR-PIT. Nagaya and colleagues report that NIR-PIT using anti-PSMA Ab-photoabsorber conjugate induced therapeutic effects against a PSMA-expressing prostate cancer in animal models. NIR-PIT could become a new treatment modality for primary and local-recurrent prostate cancer that could be readily translated to humans.Aberrant Notch signaling is critical in the initiation and maintenance of the neoplastic phenotype in many human neoplasms. It has long been appreciated that Notch functions as a transcriptional activator and establishes context dependent transcription cascades. What has been missing in the understanding of Notch-mediated transcriptional regulation is how Notch induces gene repression. Han and colleagues provide strong evidence that Notch directly recruits LSD1 and PRC2 to target promoters, which results in transcriptional repression. Not only does this study provide a novel paradigm of Notch signaling but also provides a rationale for developing new therapeutic strategies for Notch-dependent cancers.Prior work reported a large pool of small extrachromosomal circular DNA, microDNA, in normal tissues and cancer cell lines. Kumar and colleagues have now examined whether these circles of DNA, released from cells, can be detected in the blood. MicroDNA are found in the blood, and are released from cancers into the blood. Liquid biopsy is an experimental method being developed to detect cancers by examining the circulating cell-free linear DNA in the blood. These results suggest that circles of DNA are a new pool of circulating DNA that can be specifically examined in liquid biopsies.Diffuse intrinsic pontine glioma (DIPG) is an incurable childhood brain cancer whose hallmark mutation is H3K27M. Prior work unraveled that H3K27M inhibits polycomb repressive complex 2 (PRC2), an H3K27 methyltransferase complex. However, the genes downstream of H3K27M that contribute to tumorigenesis are not known. Here, using mouse genetics it is revealed that p16 (CDKN2A) is a target of H3K27M. The mechanism of p16 repression is unclear but involves aberrant histone and DNA methylation at the p16 promoter. Strikingly, the pro-tumorigenic effects of H3K27M were absent in mice with p16/p19 deletion, suggesting that restoring p16 levels is a promising therapeutic strategy.

PDE-5 inhibitors should be used post radical prostatectomy as erection function rehabilitation? | Opinion: No.

The advancement and refinement in prostate cancer detection and treatment mo-dalities have contributed to a younger patient population undergoing radical prostatec-tomy (RP) (1). Although it is effective in treating prostate cancer, radical prostatectomy has also been shown to compromise erectile function (EF), and therefore the patient’s quality of life and general well being (2). Alemozaffar et al. (3) attempted to predict erectile function after prostate cancer patients undergoing RP, external radiotherapy and brachytherapy. Pretreatment sexual health related quality of life score, age, serum prostate-specific antigen level, race/ethnicity, body mass index and intended treatment details were associated with functional erections 2 years after treatment. They found that 48% of patients (n=1027) with functional erections prior to treatment reported erectile dysfunction 2 years after treatment. In the prostatectomy cohort, 60% of patients with prior functional erections reported erectile dysfunction, along with 42% and 37% of the external radiotherapy and brachytherapy cohorts, respectively. The Prostate Cancer Outcomes study revealed 60% of men experienced self-reported erectile dysfunction 18 months after radical prostatectomy, and only 28% of men reported erections firm enough for intercourse at a 5-year follow-up (4). Many urologists believe more patients would be willing to undergo surgical treatment if it were not for the possibility of developing postoperative ED (2). The discovery of the neurovascular bundle sparing technique by Dr. Patrick Walsh enabled urologists to provide hope of regaining erectile function after radical prostatectomy (5). However, despite meticulous dissection to preserve the neurovascular bundle, there is evi-dence that neuropraxia, ischemic and hypoxic nerve insults, fibrotic remodeling, and apopto-sis of cavernous smooth muscle contribute to post-surgery erectile dysfunction (6).

PROSTATE CANCER;

Background: Androgen deprivation therapy (ADT) with luteinizing hormonereleasing hormone agonists (LHRHa) is a major treatment modality for prostate cancer (PC),particularly advanced disease. LHRHa induced hypogonadism promotes bone loss, leading toosteoporosis and heightened fracture risk. Most previous studies on skeletal impact of LHRHaemployed bone mineral density (BMD) testing. Serum bone-specific alkaline phosphatase(BSAP), an established bone biomarker, is reflective of changes in skeletal metabolism whichprecede BMD changes. In postmenopausal women, serum BSAP has been associated withfracture risk irrespective of BMD. Setting: Charing Cross Hospital, London, United Kingdom.Methods: We assessed early changes in serum BSAP levels of patients with non-metastaticPC (n=9) undergoing LHRHa therapy. Serum testosterone and estradiol concentrations werealso measured. Samples were taken at baseline before the start of treatment and three monthsafterward. Comparisons were made with blood samples taken at similar time points for agematchedcontrols without PC (n=9). Results: No significant difference in BSAP levels wasseen between groups (p=0.242). Testosterone and estradiol levels were significantly reducedfollowing treatment (p=0.000). No correlation was observed between serum BSAP and serumtestosterone (R=0.187, p=0.276) or serum estradiol (R=0.055, p=0.75). Conclusions:Changes in serum BSAP levels may not be evident as early as 3 months following ADT withLHRHa. The study was limited by the small sample size and use of serum BSAP only whichis one of the many bone markers. A larger study using multiple bone markers is warranted todetermine early effects of LHRHa treatment on bone metabolism.

MP83-07 N-TERMINAL TARGETING OF ANDROGEN RECEPTOR BY EPI-001 IN COMBINATION WITH AUTOPHAGY INHIBITORS ENHANCES THE ANTI-TUMOR EFFECT IN LNCAP PROSTATE CANCER CELLS

You have accessJournal of UrologyProstate Cancer: Basic Research & Pathophysiology II1 Apr 2017MP83-07 N-TERMINAL TARGETING OF ANDROGEN RECEPTOR BY EPI-001 IN COMBINATION WITH AUTOPHAGY INHIBITORS ENHANCES THE ANTI-TUMOR EFFECT IN LNCAP PROSTATE CANCER CELLS Benedikt Kranzbühler, Souzan Salemi, Tullio Sulser, and Daniel Eberli Benedikt KranzbühlerBenedikt Kranzbühler More articles by this author , Souzan SalemiSouzan Salemi More articles by this author , Tullio SulserTullio Sulser More articles by this author , and Daniel EberliDaniel Eberli More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.2575AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Multiple androgen receptor (AR) dependent and independent resistance mechanisms limit the efficacy of current castration resistant prostate cancer (CRPC) treatment modalities. EPI-001 is a novel N-terminal domain (NTD) binding AR targeting component with the promising ability to block constitutively active splice variants; a major resistance mechanism in CRPC. Autophagy a conserved lysosomal degradation pathway, is a survival mechanism in cells exposed to anti-cancer treatment. We hypothesized that also a promising NTD-AR treatment may lead to up-regulation of autophagy, which can be targeted by a combination therapy with autophagy inhibitors. METHODS The human prostate cancer cell line LNCaP was cultured in steroid-free medium. Cells were treated with different concentrations of EPI-001 (10, 25, 50uM) and in combination with autophagy inhibitors chloroquine (CHQ, 20uM) or 3-methyladenine (3MA, 5mM). Viability was assessed by WST-1-assays after 1, 3 and 7 days. AnnexinV and Propidium Iodide were used to measure apoptosis and necrosis on day 7 after treatment. Autophagic activity was monitored on protein levels by western blot (WB) and immunocytochemistry for the expression of LC3-I/II, Atg5 and Beclin1. In addition, autophagosome increase was detected by Autodot staining. RESULTS Treatment with EPI-001 resulted in a dose dependent reduction of cell viability up to 50% with 50uM EPI-001 on day 7. At the same time apoptosis increased by 11.53% and necrosis by 3.74% compared to the control. Combination of 50 uM EPI-001 with autophagy inhibitors led to a further significant reduction of cell viability up to 40% for CHQ and 28% for 3MA. Assessment of autophagy levels in EPI-001 treated cells by WB showed an increase of LC3-II in a dose dependent manner. No Change in Beclin1 expression was seen. Immuncytochemistry detected a significant increase of Atg5 and pronounced LC3-II punctuation in EPI-001 treated cells. This was supported by an increase in autophagosome punctuation observed by Autodot staining. CONCLUSIONS Our data demonstrate that the treatment with EPI-001 leads to increased autophagic activity in LNCaP prostate cancer cells. Combination of N-terminal androgen receptor blockage with simultaneous autophagy inhibition increases the antitumor effect of EPI-001 in vitro. This may offer a promising strategy to overcome resistance mechanisms in castration resistant prostate cancer. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e1108 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Benedikt Kranzbühler More articles by this author Souzan Salemi More articles by this author Tullio Sulser More articles by this author Daniel Eberli More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

High Dose Rate Brachytherapy as Monotherapy for Localised Prostate Cancer: Review of the Current Status

The aim of this article is to review and present the published data on high dose rate (HDR) brachytherapy as monotherapy in the treatment of localised prostate cancer. A search and review of the literature was carried out on PubMed and MedLine using the medical subject headings ‘high-dose-rate, brachytherapy, prostate cancer, monotherapy’ as search terms. The search yielded more than 100 articles and abstracts published between 2000 and 2016. Only original clinical data on HDR monotherapy reporting oncological outcomes were included. When more than one series from the same institution were identified, the most recent one encompassing the largest patient number was considered for analysis. For citation crosscheck, the ISI web of science database was used employing the same search terms. Data tables were generated and summary descriptions created. The main outcome parameters used were biochemical control and toxicity scores. Fifteen articles comprising 3546 patients reported clinical outcome and toxicity, with follow-up ranging from median 1.4 to 8.0 years. A variety of dose and fractionation schedules were described, including 19.0 Gy as a single fraction to 54.0 Gy in nine fractions. Biochemical control rates ranged from 66 to 100% in low-risk, 63 to 98% in intermediate-risk and 81–93% in high-risk patients. Late grade 3 genitourinary and gastrointestinal toxicity was 0–16% and 0–2%, respectively. The reported potency preservation rates ranged from 60 to 90%. In conclusion, high biochemical control and low complication rates are reported with HDR monotherapy. It is a safe and effective local treatment modality for organ-confined prostate cancer with reproducible high-quality dosimetry.

Permanent seed brachytherapy for low risk prostate cancer, long term outcome, and urinary toxicity.

66 Background: Low dose rate seed brachytherapy is an established treatment modality for low risk prostate cancer (CaP). Herein, we report long term biochemical control and urinary toxicity from a single institution. Methods: Data from a prospectively-collected institutional database was used, completed with retrospective chart reviews. All patients with low-risk CaP (NCCN criteria) who underwent ultrasound-guided permanent iodine-125 brachytherapy from March 1999 to December 2005 were included. Urinary function was evaluated by the International Prostate Symptom Score (IPSS). PSA relapse was defined by Phoenix Criteria (nadir + 2 ng/ml). Time to IPSS return-to-baseline score ±3 was recorded. Results: 582 patients with a median age of 64 years were included. Median initial PSA was 5.5 ng/ml (0.3-10). 66% and 34% were T1 and T2a, respectively. Gleason score was 6 (96%) and &lt; 6 (4%). Prescription dose was 145Gy, with a median V100 coverage of 94% (IQR [interquartile range] 89-97%) and median D90 of 157Gy (IQR 144-171 Gy). With a median follow up of 131 months (IQR 94-149 months), 27 patients showed biochemical failure (4.6%), and PSA bounce was detected in 38 cases (7%). Biochemical progression-free rates were 97% (96-98%), 96% (94-97%), and 94% (91-96%) at 5, 10, and 15 years, respectively. Median PSA level at 5, 10 and 15 years was 0.06, 0.05 and 0.018 ng/ml, respectively. PSA relapses were observed out to 148 months. At 1, 5, 10 and 15 years, 5.5%, 16.5%, 39.5% and 89.2% of patients were lost to PSA follow up. Median baseline IPSS score was 5. In 515 (88.5%) patients IPSS returned to baseline, with a median time to return-to-baseline of 9 months. The proportion of return-to-baseline at 1, 2, 5, and 10 years was 62%, 75%, 88%, and 90%, respectively. 22 (4%) patients required post-implant urinary catheter. After 3, 6 and 12 months, 9 (1.5%), 6 (1%) and 4 (0.7%) patients continued to be catheterized. Conclusions: Within the limits of retrospective analysis, permanent seed brachytherapy for low risk prostate cancer is an effective treatment modality with low urinary toxicity. Treatment resulted in excellent long-term biochemical control although late relapses were observed.

Assessment and Comparison of Homogeneity and Conformity Indexes in Step-and-Shoot and Compensator-Based Intensity Modulated Radiation Therapy (IMRT) and Three-Dimensional Conformal Radiation Therapy (3D CRT) in Prostate Cancer

Intensity modulated radiation therapy (IMRT) and three-dimensional conformal radiation therapy (3D CRT) are two treatment modalities in prostate cancer, which provide acceptable dose distribution in tumor region with sparing the surrounding normal tissues. IMRT is based on inverse planning optimization; in which, intensity of beams is modified by using multileaf collimators and also compensators with optimum shapes in step and shoot (SAS) and compensator-based method, respectively. In the recent study, some important parameters were compared in two IMRT and 3D CRT methods. Prescribed dose was 80 Gy for both IMRT procedures and 70 Gy for 3D CRT. Treatment plans of 15 prostate cancer candidates were compared to target the minimum dose, maximum dose, V 76 Gy (for IMRT plans) V 66.5 Gy (for 3D CRT), mean dose, conformity index (CI), and homogeneity index (HI). Dose conformity in compensators-based IMRT was better than SAS and 3D CRT. The same outcome was also achieved for homogeneity index. The target coverage was achieved 95% of prescribed dose to 95% of planning target volume (PTV) in 3D CRT and 95% of prescribed dose to 98% of PTV in IMRT methods. IMRT increases maximum dose of tumor region, improves CI and HI of target volume, and also reduces dose of organs at risks.

Minimizing urinary toxicity in daily prostate stereotactic body radiotherapy with urethra dose constraints.

e16614Background: Stereotactic body radiotherapy (SBRT) is an evolving and promising treatment modality for prostate cancer but without mature data compared with other definitive therapies. There i...

A Hand-Held Assistant for Semiautomated Percutaneous Needle Steering.

Permanent prostate brachytherapy is an effective and popular treatment modality for prostate cancer in which long needles are inserted into the prostate. Challenges associated with manual needle insertion such as needle deflection limit this procedure to primarily treat the entire prostate gland even for patients with localized cancer. In this paper, we present a new semiautomated hand-held needle steering assistant designed to help surgeons improve needle placement accuracy. Regular clinical brachytherapy needles are connected to a compact device that the surgeon holds. As the surgeon inserts the needle, the device rotates the needle base on a measured and calculated basis in order to produce a desired trajectory of the needle tip. A novel needle-tissue interaction model and a steering algorithm calculate such control actions based on ultrasound images of the needle in tissue. The assistant can also apply controlled longitudinal microvibrations to the needle that reduce needle-tissue friction. Experimental validation of the proposed system in phantom and ex-vivo biological tissue report an average needle targeting accuracy of 0.33 mm over 72 needle insertions in 12 different experimental scenarios. We introduce a new framework for needle steering in prostate brachytherapy in which the surgeon remains in charge of the needle insertion. The device weighs 160 g, making it easy to incorporate with current insertion techniques. Expected benefits of the proposed system include more precise needle targeting accuracy, which can result in improved focal treatment of prostate cancer.

Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.

S&T-54 NOVEL MOLECULAR TARGETS AKR1C2 IS ASSOCIATED WITH TESTOSTERONE METABOLISM IN PROSTATE CANCER AFTER TREATMENT OF CURCUMIN

INTRODUCTION AND OBJECTIVES: Radical prostatectomy (RP), intensity modulated radiation therapy (IMRT) and brachytherapy (BT) are three major definitive treatment modalities for localized prostate cancer in recent years. While a lot of technical progress are seen in this decade, patients with localized prostate cancer are often struggling with making a decision of their treatment. It might be due to luck of information in terms of comparing the outcomes among these modalities since only few reports are seen in the literature. Propensity score matching analysis in nonrandomized studies is to balance the treatment and comparison groups on observed preintervention characteristics. Though it may not be considered an equivalent to randomized trial, it reduces to a minimum the inherent treatment selection bias associated with retrospective data. We analyzed the results of three treatment modalities in a single institution in Japan. METHODS: From Jan 2004 to Aug 2014, a group of 1943 patients with clinically localized prostate cancer treated with RP (454pts), IMRT (343pts) and BT(1146pts) were identified in our institution. The records of RP (n1⁄4362), IMRT (n1⁄4225) and BT (n1⁄4826) patients with a minimum of 2 years of follow-up (total 1413) were reviewed. Propensity scores were calculated using multivariable logistic regression based on the covariates including patient’s age, preoperative PSA, Gleason score, number of positive cores, clinical T stage. Each cohort were categorized according to NCCN risk classification and biochemical outcomes plus overall survival were examined. Biochemical failure was defined as RP: PSA >0.2ng/ml, IMRT, BT: nadir PSA level +2ng/ml. RESULTS: Median follow-up was 69.1 months (mo) for RP, 51.0 mo for IMRT and 57.3 mo for BT patients. After adjustment of propensity scores, a total of 260 patients (130 each) and 428 patients (214 each) were matched for RP vs IMRT cohort and RP vs BT cohort, respectively. Kaplan-Meier analysis did not show any statistically significant differences in terms of overall survival in these two cohorts (RP vs IMRT:p1⁄40.421, RP vs BT:p1⁄40.764). Regarding biochemical failure free survival, there was statistically significant differences in all risk group in RP vs IMRT cohort (High-risk: p1⁄40.000, Intermediate-risk: p1⁄40.001, Low-risk: p1⁄40.007), while significant differences were observed in low (p1⁄40.003), intermediate (p1⁄40.006) risk group among RP vs BT cohort. CONCLUSIONS: Our mid-term outcomes for localized prostate cancer using propensity score analysis demonstrated no significant differences in overall survival. Despite the difference of biochemical failure definition, IMRT and BT improved biochemical failure free survival compared to RP with excellent tumor control in Japanese people

Outcomes and patient-related reported urinary toxicity of low dose rate brachytherapy for localized prostate cancer.

29 Background: Brachytherapy (BT) is a common treatment modality for localized prostate cancer (LPCa). Here we report our institutional outcomes and patient-reported genitourinary (GU) toxicity following BT for LPCa. Methods: Medical records of patients with LPCa treated with low dose rate (LDR) BT at our institution from 1997-2011 were reviewed. BT prescriptions were 145 Gray (Gy) and 109Gy for mono- and combined iodine 125 (125I) therapy, and 125Gy and 100Gy for mono- and combined palladium 103 (103Pd) therapy. Biochemical failure was defined by the Phoenix definition. Kaplan Meier curves were used to compare biochemical relapse-free survival (bRFS), metastasis-free survival (MFS), and overall survival (OS). Patient-reported GU toxicity was evaluated by the American Urological Association Symptom Score (AUAS), and results binned into three time intervals, 1, 6, and 12 months post-BT. Repeated measures analysis determined a trend in AUAS score over time. Effect of age as a continuous variable, prostate specific antigen, Gleason score, clinical T stage, combined external beam radiotherapy + BT and use of neoadjuvant androgen deprivation therapy (nADT) on AUAS score was determined. Results: Of 459 patients identified, 400 received BT monotherapy and 8% received nADT. Median follow-up was 5.8 years. Nine-year bRFS, MFS, and OS were 92.8%, 97.9%, and 79.7%. Pretreatment AUAS scores were available for 252 patients. For 69 patients with all four values, median baseline AUAS scores rose from 6 to 14 at one month following BT (p &lt; 0.0001). AUAS scores did not change from one-month to 6 months post-BT (p = 0.99), but decreased to a median of 8 (p &lt; 0.0001) by 12 months post-BT. In the 69 patients with all values, no factors were found significant for change in AUAS scores. For 252 patients with pre-treatment AUAS and at least one additional value (assuming values missing at random), analysis revealed older age and use of nADT were associated with higher AUAS scores at all time points. Conclusions: LDRBT for LPCa offers excellent bRFS, MFS, and OS. AUAS scores rose in the first 6 months following BT but returned to pre-treatment baseline by 12 months post-BT. Older age and nADT use may be associated with higher AUAS scores.